Basophils are specialized, circulating polymorphonuclear cells which produce and store several pharmacologically active mediators. The release of these mediators from basophils is stimulated by antibody (IgE)-antigen interaction, activated complement fragments and supernatants from stimulated twenty-four hour mononuclear cell cultures. The morphologic demonstration of pronounced basophilic infiltration in several types of cell-mediated immune responses suggests that basophils participate in these reactions. In vitro production of a factor chemotactic for basophils, and of an activity that stimulates histamine release from basophils has been demonstrated. A better understanding of these factors may explain the temporal sequence of basophil accumulation and subsequent degranulation. The applicant has recently reported the discovery of an activity produced by mononuclear cell cultures which stimulates the release of histamine from human basophils (HRA). The physio-chemical properties of HRA, including molecular weight, heat stability and enzyme sensitivity, will be determined. Preparation and culture of various highly enriched cell types will clarify the cellular source of the activity. Factors affecting production, especially various mitogens, and helper cell-requirements will be examined. The response of basophils to HRA and conditions influencing the activation of these cells and subsequent release of histamine will also be investigated. The nature and properties of HRA will be compared with soluble lymphocyte-derived mediators important in cell-mediated immune reactions. These studies will probe the possible role of HRA in the elicitation of cutaneous basophil hypersensitivity.